title: Overexpression of integrin-linked kinase promotes lung cancer cell migration and invasion via NF-κB-mediated upregulation of matrix metalloproteinase-9.
abstract: Integrin-linked kinase (ILK) is a highly conserved serine-threonine protein kinase which has been implicated in the regulation of various cellular processes. Previously, we have demonstrated that overexpression of ILK correlates with malignant phenotype in non-small cell lung cancer. Furthermore, forced overexpression of ILK promotes lung cancer cell invasion and migration. However, the molecular mechanisms by which ILK enhances the invasive phenotype of lung cancer cells are still not fully understood. In the present study, we found that overexpression of ILK stimulated matrix metalloproteinase-9 (MMP-9) expression and activity in lung cancer cells. ILK-induced cell migration and invasion were significantly inhibited by MMP inhibitor doxycycline as well as by anti-MMP-9 neutralizing antibody. In addition, overexpression of ILK induced phosphorylation and nuclear translocation of nuclear factor-κB (NF-κB) subunit p65. Finally, upregulation of MMP-9 was severely abolished by either BAY 11-7028, a specific NF-κB inhibitor, or small interfering RNA targeted to NF-κB p65 in ILK overexpression cells. Taken together, these findings suggest that ILK promotes lung cancer cell migration and invasion via NF-κB-mediated upregulation of MMP-9.
authors.affiliation: Department of Respiratory Medicine, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, People’s Republic of China.
authors.forename: Mingjing
authors.initials: M
authors.lastname: Zhao
authors.forename: Ying
authors.initials: Y
authors.lastname: Gao
authors.forename: Lingling
authors.initials: L
authors.lastname: Wang
authors.forename: Shuo
authors.initials: S
authors.lastname: Liu
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.forename: Lie
authors.initials: L
authors.lastname: Ma
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ling
authors.forename: Shitao
authors.initials: S
authors.lastname: Mao
authors.forename: Xiaoge
authors.initials: X
authors.lastname: Wang
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology; D001483:Base Sequence; D017931:DNA Primers; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D020780:Matrix Metalloproteinase 9 / Q000276:immunology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation; D000099200:Scaffold Protein ILK
chemical_list: D057134:Antibodies, Neutralizing; D017931:DNA Primers; D020780:Matrix Metalloproteinase 9; D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK
keywords: integrin-linked kinase; invasion; lung cancer cell; matrix metalloproteinase-9; migration; nuclear factor-κB